Synaptic inhibition shapes the activity of neuronal populations in space and time. Basket cells, a class of inhibitory interneurons which synapse specifically on the somata of principal cells, provide strong local inhibition to balance afferent excitation. However, the specific means by which they control the activity of their target neurons is poorly understood. This proposal addresses the role of a unique population of basket cells: cannabinoid sensitive basket cells. Our preliminary data suggest that cannabinoid sensitivity defines a distinct network of hippocampal basket cells with unique functional properties. Cannabinoid sensitive basket cells are only weakly and transiently excited such that, under basal conditions, they are responsible for only a minority of inhibition in the hippocampus. However, application of neuromodulators such as opioids can shift the balance of inhibition in favor of cannabinoid sensitive interneurons. Thus, an understanding of the role of these interneurons will help to elucidate how both cannabinoids and opioids modulate network activity. Further, a deeper insight into how a balance between excitation and inhibition is dynamically maintained may contribute to the development of therapies aimed at preventing epileptogenesis in cortical areas.